同种异体CAR-T细胞的研究进展

Research progress in allogeneic CAR-T cells

自体嵌合抗原受体(chimeric antigen receptor,CAR)-T细胞技术已经改变了B细胞恶性淋巴瘤的治疗前景。然而,由于获批用于临床治疗的CAR-T细胞必须定制而成,因此限制了其在临床上的大规模应用。探索能够实现"现货供应"和细胞产品标准化、多抗原靶向以及低工业生产成本等优势的同种异体CAR-T细胞技术,是目前过继免疫疗法的主攻方向之一。然而,同种异体CAR-T细胞可能会导致危及生命的移植物抗宿主病(graft-vs-host disease,GvHD),并可能被宿主免疫系统迅速清除。本文对如何采用基因编辑技术规避GvHD和异源CAR-T细胞的免疫原性,以及当前同种异体CAR-T细胞的临床和基础研究进展进行综述。经过改良的下一代同种异体CAR-T细胞或将为复发或难治性恶性肿瘤的治疗开辟坦途。

Chimeric antigen receptor (CAR)-T cells have changed the therapeutic prospects of hematological malignancies.However,CAR-T cells approved for clinical use must be produced on a customized basis,which limits their large-scale clinical application.Exploring the allogeneic CAR-T cell technology that can achieve "off-the-shelf supply",cell product standardization,multiple antigen targeting,and low industrial production cost is one of the main directions of adoptive immunotherapy.However,allogeneic CAR-T cells may cause life-threatening graft-vs-host disease (GvHD) and may be quickly cleared by the host immune system.In this paper,the progress in evading GvHD and heterologous CAR-T cell immunogenicity based on gene editing technology,and the current clinical and research on heterologous CAR-T cells are reviewed.The improved next-generation allogeneic CAR-T cells may pave the way for further breakthroughs in recurrent or refractory malignant tumors.